This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The conventional paradigm of innate immunity suggests that relatively few pattern-recognition receptors (PRRs) are needed for non-self recognition. PRRs are able to recognize highly conserved pathogen-associated molecular patterns (PAMPs) present on the surface of pathogens, no matter how great the differences among the pathogens are. Based on the emerging studies from different labs, this view seems incomplete. Our recent work on the diversification of fibrinogen related protein (FREP) genes provides the first evidence in invertebrates for the diversification of innate defense molecules through a novel mechanism. The goal of this project is to study the mechanism of diversification of an immune-related gene (FREP) family in an invertebrate host and to investigate molecular aspects of the interaction between this host and relevant parasites. The specific goals of the project are to determine underlying mechanisms generating diversity of FREP genes observed in our previous investigations, and to develop RNA interference (RNAi) to assess FREP functions. Understanding the mechanism of diversification and function of FREPs, will broaden our understanding of invertebrate innate immunity in general, and snail internal defense in particular. Ultimately, the study will have benefits for the control of schistosomiasis, a snail-borne disease that affects 200 million people world wide.